The effect of serotonin on active electrolyte transport was evaluated in vitro in epithelial sheets of rabbit ileum, gallbladder, and colon under short-circuited conditions. Serotonin added to the serosal surface of rabbit ileum caused a dose-dependent short-lived increase in short-circuit current and a more prolonged equal effect on net Na and Cl fluxes. The latter consisted primarily of inhibition of mucosal-to-serosal fluxes of both Na and Cl. In addition serosal serotonin decreased ileal Na influx from the mucosal solution into the epithelium, suggesting an effect on Na absorption. Serotonin did not alter all aspects of ileal absorptive function and did not affect glucose-dependent Na absorption. Consistent with serotonin acting by inhibiting NaCl absorption in the ileum, serotonin induced equal inhibition of net Na and Cl absorption in rabbit gallbladder (which has a linked Na and Cl absorptive process) but had no effect on rabbit colon (which lacks a linked Na and Cl absorptive process). In addition, adenosine 3',5'-cyclic monophosphate and serotonin both appeared to alter the same ileal NaCl absorptive process, since following stimulation of ileal secretion with the maximum concentration of theophylline, addition of serotonin did not cause any further effects.

The in vitro antisecretory effects of the alkaloid berberine (1.0 mM) on intestinal ion secretion and mucosal adenylate cyclase and Na-K-ATPase activities were studied in the rat ileum. Mucosal berberine did not alter the individual basal net ion fluxes and basal adenylate cyclase activity but decreased short-circuit current (Isc) and increased the net absorption of chloride plus bicarbonate. In the cholera toxin-treated tissue, mucosal berberine stimulated absorption of Na and Cl and inhibited the increased adenylate cyclase activity but did not change the specific Na-K-ATPase activity, whereas serosal berberine stimulated Na secretion and decreased Isc. Mucosal berberine also decreased Isc, increased Cl permeability, and reversed the ion secretion induced by dibutyryl cyclic AMP, the heat-stable enterotoxin of Escherichia coli, and methylprednisolone administration. The antisecretory effects of mucosal berberine may be explained by stimulation of a Na-Cl-coupled absorptive transport process. The mechanism of action of serosal berberine remains to be elucidated. However, it is clear that mucosal berberine affects intestinal ion transport by mechanisms different from stimulation of the Na pump and probably at a step distal to the production or degradation of cyclic AMP or cyclic GMP.

The relationships among ion current, membrane potential difference, and resistance of an epithelium are studied. The short-circuit technique introduced by Ussing and Zerahn does not completely short circuit the epithelium if the series resistance parallel to the cell layer between the voltage electrodes is not properly compensated. The residual potential difference across the epithelial cell layer in the "short-circuit state" is proportional to both the measured short-circuited small intestinal mucosa the villus and crypt areas are hypo-polarized to different degrees rather than simultaneously hyper- and hypo-polarized. Short-circuiting the whole tissue reduces but does not abolish the passive net ion movement across the tissue. Measurements of the electrical properties of the whole and denuded rat distal small intestine in HCO3-Ringer solution containing 10 mM glucose reveal that the measured short-circuit current has under-estimated approximately 33% of the true short-circuit current and that the passive net Na flux from serosa to mucosa and Cl flux from mucosa to serosa are not negligible in the "short circuit state."

To investigate the characteristics of intestinal ion and fluid secretion induced by the adherent, effacing enteropathogenic Escherichia coli strain RDEC-1, we infected weanling rabbits with 10(7)-10(8) RDEC-1 organisms and then studied cecal ion transport under short-circuit conditions in Ussing chambers. Results in tissues with confluent adherent organisms were compared with those in uninfected ceca and in ceca stimulated with dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP). The short-circuited cecum normally absorbed Na and Cl, secreted bicarbonate (as represented by the residual ion flux), and displayed a high rate of nondiffusional Na and Cl transport. RDEC-1 infection did not alter the short-circuit current (Isc), but it increased the conductance (Gt), decreased the potential difference (PD), abolished net Na absorption, and reversed Cl absorption to secretion. The changes in Na and Cl net fluxes may be explained by inhibition of a Na-Cl linked absorptive process. In contrast, DBcAMP significantly increased the Isc, PD, and Gt, decreased net Na flux, and abolished net Cl absorption by stimulating electrogenic Cl secretion. These results suggest that RDEC-1-induced changes in cecal ion transport are not mediated by cAMP. The reduction in Na-Cl linked absorption is consistent with anatomic changes in the apical surfaces of absorptive epithelial characteristic of effacing enteroadherence, whereas the increased conductance is consistent with tight junction disruption seen with RDEC-1 infection.

Sodium flux from serosa to mucosa, JN, in rabbit ileum in vitro has been studied as a function of applied electrical potential at equal sodium concentrations in the bathing solutions. The results indicate that J involves two pathways, a diffusional flux through a paracellular shunt pathway and a flux that is independent of applied potential and presumably involves a transcellular pathway. The latter pathway comprises approximately 25 % of J in Ringer's solution containing 10 mM glucose and 25 mM bicarbonate. It is stimulated significantly by theophylline unaffected by removal of glucose or addition of ouabain but is reduced to negligible values by anoxia, dinitrophenol, and replacement of all chloride and bicarbonate by isethionate. Thus this component of J:L has a number of characteristics consistent with involvement in a specific secretory process mediating an electrically neutral secretory transport of sodium plus anion from serosa to mucosa. In addition to stimulating this process, theophylline significantly reduced the permeability of the paracellular shunt pathway to sodium.Recent studies on ion transport across rabbit ileum have raised certain questions about mechanisms involved in movement of ions from the serosal to the mucosal side of the tissue. For example, Frizzell and Schultz (1) have suggested that nearly all of the Na flux from serosa to mucosa across in vitro preparations of rabbit ileum occurs via the intercellular shunt pathway they have described (see also Rose and Schultz [2]). On the other hand, Powell et al. have proposed that there may be an active secretory process for Na in guinea pig ileum (3) and rabbit ileum (4, 5) that accounts for a part of the observed serosal-to-mucosal flux and that this process may be stimulated by cholera toxin (6) and theophylline (5). Such a process might be expected to involve transcellular movement of Na and would not be consistent with purely passive Na movement from serosa to mucosa via a shunt pathway. The situation is further complicated by the suggestion of Field et al. (7,8) that the THE JOURNAL OF GENERAL PHYSIOLOGY

The short-circuit current (Isc), potential difference (PD), tissue conductance (Gt), and Na and Cl fluxes in the short-circuit state across rat ileum were studied in Ussing chambers using a variety of bathing solutions. In Ringer solution, Isc exceeded net Na absorption and net Cl secretion occurred. Addition of 10 mM glucose increased Isc, PD, Gt, and net Na absorption, which accounts for 70% of the increase in Isc. Removal of HCO3 from Ringer solution did not alter any parameters but increased net Cl secretion due to a decrease in mucosal-to-serosal Cl flux. Reduction by 50% of the [Cl] in HCO3-free solution decreased the net Cl secretion to the level in Ringer solution and increased net Na absorption. Removal of Cl decreased Isc to the value of the net Na absorption and decreased the Na influx across the mucosal membrane by 39%. Isc and PD were near zero and net Cl absorption was observed in a Na-free solution. These results are consistent with the transport mechanism that consists of 1) an electrogenic Na absorptive process that accounts for the Isc, 2) a neutral NaCl-coupled secretory process, and 3) a system by which HCO3- secretion exchanges for Cl- absorption.

No abstract

The effect of luminal berberine hydrochloride concentration on cholera toxin-induced water and electrolyte secretion and on normal water and electrolyte transport was determined in vivo in the cannulated, perfused rat ileum using [14C]polyethylene glycol as a nonabsorbable marker. Berberine reduced the cholera toxin-induced secretion of water, Na, Cl, and calculated residual ion (primarily HCO3) in a concentration-dependent manner. The effect of berberine on cholera toxin-induced ileal secretion was evident 60-80 min after exposure and was reversed 60-80 min after removal of berberine from the perfusate. Mild changes in mucosal histology (villous tip edema) due to cholera toxin were also reversed by berberine. Berberine did not significantly alter normal ileal water and electrolyte transport.